METTL1-mediated m⁷G modification of Arg-TCT tRNA drives oncogenic transformation.

ABSTRACT: The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m⁷G) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m⁷G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. Mechanistically, we find increased abundance of m⁷G-modified tRNAs, in particular Arg-TCT-4-1, and increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon. Accordi

SUBMITTER: Orellana EA 

PROVIDER: S-EPMC8380730 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature